Invasive Pulmonary Aspergillosis Associated with Infliximab Therapy

Abstract

A 25-year-old man with fistulizing Crohn's disease began to have high fever, dyspnea, and a productive cough five days after he received a single intravenous dose of 5 mg of a monoclonal antibody against tumor necrosis factor α (anti–TNF-α antibody; infliximab, Centocor, Malvern, Pa.) per kilogram of body weight. His current medications did not include corticosteroids or other immunosuppressive drugs. His chest roentgenogram showed massive, bilateral infiltrates, and laboratory examination revealed an elevated C-reactive protein value and leukocytosis. He received treatment with intravenous broad-spectrum antibiotics. Within 24 hours after admission, respiratory insufficiency developed. Ventilatory support and extracorporeal membrane oxygenation were needed to achieve adequate oxygenation. On day 7, Aspergillus fumigatus was grown from a culture of tracheal secretions but was considered clinically nonsignificant. Treatment with high-dose corticosteroids was started because of adult respiratory distress syndrome. On day 13, cultures of tracheal secretions and bronchoalveolar-lavage fluid repeatedly yielded A. fumigatus, and treatment with liposomal amphotericin B (3 mg per kilogram per day) was started. The results of bacteriologic and virologic examinations remained negative. The results of analyses for TNF-α and aspergillus antigen on serial plasma samples were negative. A hemothorax developed. Samples obtained during a thoracotomy on day 22 showed growth of A. fumigatus, and results of antigen testing were positive. Despite the intensive treatment, the patient died from multiorgan failure and septic shock on day 24. Postmortem examination of lung tissue showed invasive growth of septated hyphae, and cultures revealed A. fumigatus.